Albert S. Braverman

Treatment of advanced bladder carcinoma with irradiation and concomitant 5-fluorouracil infusion

Nineteen patients with locally advanced bladder cancer were treated with irradiation and concomitant 5‐fluorouracil intravenous infusion with or without bolus mitomycin. Eighteen of the 19 patients were evaluated for local response. Eleven of the 18 patients (61%) obtained a complete local response within 3 to 6 months. An additional five patients (28%) showed tumor regression to a superficial state controlled by local transurethral resection and intravesical chemotherapy making the overall local clearance rate 16/18 (89%). The remaining two patients (11%) required salvage cystectomy for persistant disease and presently show no evidence of disease. Nine patients have died. Two patients died of intercurrent disease, six patients died of metastatic disease, and one patient who died from regional disease showed no evidence of local bladder tumor at the time of death. Berkson‐Gage life‐table analysis yields an adjusted survival of 62.5% at 5 years. Late complications included five patients with hemorrhagic cystitis, two patients with a contracted bladder, and one patient with a hemorrhagic radiation proctitis. Cancer 59:710‐714, 1987.

Response of cold-rectal hepatic metastases to concomitant radiotherapy and intravenous infusion 5 fluorouracil

Twenty-three patients with colo-rectal hepatic metastases were retrospectively reviewed after completing treatment with split course liver irradiation and continually infused concomitant intravenous 5-fluorouracil. Although no patient attained a complete response, an objective partial response was documented in 15 (Responders). The Responders had a median survival of 45 weeks whereas Non-responders had a median survival of 17 weeks. Patients with metastatic disease solely in the liver or those with a Karnofsky performance score (k.p.s) of over sixty, had a median survival of 49 weeks. Patients with multiple organ metastatic involvement had a median survival of 25 weeks and those with a Karnofsky with less than 60 had a median survival of 27 weeks. (p values of 0.006 and 0.03, respectively.) The overall survival of the group completing treatment was 30 weeks, and 19 patients (83%) achieved subjective palliation. The patients tolerated therapy well. There was minimal hematological toxicity; 3 patients developed a leucocyte count of less than 2000 and 1 developed a platelet count of 30,000. The palliation and prolongation of survival attained with minimal complications suggest that adjuvant liver irradiation with concomitant infusion 5-fluorouracil radiosensitization may be an option to offer patients identified to be at high risk of developing subclinical liver disease.

Prognoses of T4 breast cancer subsets

BackgroundThe relative prognoses of subsets of patients with T4 breast tumors, since the advent of neoadjuvant therapy, are unknown, although inflammatory carcinoma (T4d) is considered to have the worst prognosis.MethodsSubsets of T4 patients were analyzed for the incidence of distant metastases at presentation (M1; n=263). T4M0 patients treated with neoadjuvant therapy (n=126) were analyzed for relapse-free survival (RFS). T4d tumors with (Cut/CW+) and without (Cut/CW−) skin nodules, posterior fixation, or both were analyzed separately.ResultsFewer patients with T4d (Cut/CW−) tumors had distant metastases at presentation than T4d (Cut/CW+) patients or T4b and T4c patients (P=.001, .001, and .009, respectively). RFS was longer for T4b patients than for T4c patients (P=.018) or T4d (Cut/CW+) patients (P=.003). RFS of the T4d (Cut/CW+) patients was shorter than for T4d (Cut/CW−) patients (P=.050).ConclusionsThe incidence of distant metastases at presentation was lowest, and RFS was longest, for patients with T4d tumors not grossly involving the skin or posterior structures. Patients whose tumors grossly invaded both skin and posterior structures (T4c) or those with T4d tumors grossly invading either most frequently presented with distant metastases and had the shortest RFS.

Accurate Prediction of the Amount of In Situ Tumor in Palpable Breast Cancers by Core Needle Biopsy: Implications for Neoadjuvant Therapy

Background: Neoadjuvant chemotherapy facilitates breast conservation in stage II breast cancer patients, whose primary tumors are assumed to be invasive because they are palpable. However, chemotherapy may not be indicated in the minority of patients whose clinically T2 tumors are completely or predominantly in situ. Almost all previous studies of core needle biopsy in breast cancer have been concerned with nonpalpable, mammographically detected tumors, and none have evaluated its ability to quantitatively determine the amounts of in situ and invasive disease.Methods: From September, 1992 to December, 1997, core needle biopsy was performed on all patients presenting to the Kings County Hospital Breast Clinic with palpable breast masses. Carcinoma was present in both core needle biopsy samples and surgical specimens subsequently obtained from 95 of 99 patients. Each specimen was evaluated for tumor type, histologic grade, and the amounts of in situ and invasive carcinoma it contained, and the results from surgical and core needle biopsy specimens from the same patients were then compared.Results: The surgical specimens of 14 patients had completely or predominantly in situ disease. Completely or predominantly invasive disease was present in 67 specimens, and the remaining 14 had significant amounts of both. The high level of agreement between the amounts of in situ and invasive disease in core needle biopsy and surgical specimens is indicated by Pearson and intraclass correlation coefficients of 0.91 (P < .001 and < .00001, respectively). Tumor type was correctly predicted by core needle biopsy in each case. Variables among these patients, including primary tumor size, interval between biopsy and surgery, or administration of neoadjuvant systemic therapy, did not alter agreement between core needle biopsy and surgical specimens.Conclusions: Core needle biopsy can identify palpable breast tumors that are predominantly or completely in situ, and, thus, avoid unnecessary neoadjuvant chemotherapy. It also can demonstrate that a tumor is predominantly invasive, but cannot rule out small invasive foci. For that purpose, complete surgical excision of the tumor is required.

Tapering and Discontinuation of Glucocorticoid Prophylaxis during Prolonged Weekly to Biweekly Paclitaxel Administration

Background: Taxanes cause hypersensitivity reactions, averted by premedication with H1 blockers and high glucocorticoid (GC) doses. Prolonged weekly taxane administration may lead to GC toxicity. Purpose: To determine whether patients not hypersensitive to initial paclitaxel (PTX) infusion after high-dose GC premedication will tolerate subsequent, prolonged PTX treatment without GC prophylaxis. Patients and Methods: In 115/122 breast cancer patients not hypersensitive to initial PTX treatment, 20 mg dexamethasone (DXM) doses were tapered by 2.0 mg/week, reaching 0 in those receiving 9 or more courses. After 4 PTX courses, diphenhydramine was administered orally, rather than intravenously. Results: PTX was administered 143 times after 2.0–5.0 mg of DXM and 357 times without DXM. A total of 46 patients received 1–40 PTX courses without DXM. None of these 115 patients experienced hypersensitivity reactions. Conclusion: Patients unreactive to their first PTX infusions, after high-dose and tapering GC premedication, may not require GC prophylaxis for subsequent PTX therapy.

T Cell Lymphoma Associated with Myelofibrosis

Myelofibrosis is most frequently associated with certain primary myeloproliferative disorders, but is rare in lymphoid neoplasms. We report the fourth case associated with T-cell lymphoma, involving bone marrow, lymph nodes and spleen. Marked extramedullary hematopoiesis was present. Myelofibrosis subsided completely with response to standard anti-lymphoma combination chemotherapy. Since lymphomatous splenic and bone marrow involvement was minimal in our patient, fibrotic bone marrows should be carefully evaluated for lymphoma.

Effective treatment of the brachial plexus syndrome in breast cancer patients by early detection and control of loco-regional metastases with radiation or systemic therapy

BackgroundIn breast cancer (BC) patients the brachial plexus syndrome (BPS) has been reported to be due to loco-regional metastases or radiation plexopathy. Associated arm edema is considered more suggestive of the latter. Radiation therapy is the only effective treatment for BPS reported.MethodsThe charts of all BC patients who presented to our clinic from 1982 to 2006 with homolateral arm pain and neurological deficits, without humerus, cervical spine, or brain metastases, were reviewed.ResultsThere were 28 patients fulfilling these criteria for BPS. Supraclavicular, axillary or chest wall metastases developed synchronously with the BPS in 26 patients; in 21 they were recurrences, found 6–94 months (median 34 months) after primary BC treatment, while in 5 others they were progressing inoperable primary tumors and nodes. Arm edema first occurred at the same time as loco-regional metastases in 19 patients. Treatment for the BPS was administered to 22 patients; it was directed at their locoregional metastases. The BPS was initially treated with radiation (8 patients) or chemo- or endocrine therapy (14 patients); 19 (86%) had partial or complete remission of pain and neurologic deficits, with an 8-month median duration.ConclusionThe BPS in BC patients is due to loco-regional metastases and is often associated with arm edema. Chemoor endocrine therapy induced the remission of pain and deficits as frequently as radiation therapy.

Evidence for Increased Proteolysis in Intact β Thalassemia Erythroid Cells

Mxh excess u chain is synthesized, but little accumlates in the erythroid ells of patients with hanozycpus B thalassda. To dew if the proteases Imam to exist in erythmid cells play a role in the destruction or alteration of any of this excess α dmin, thalassemic and nmthalassemic erythroid cells were incubated for 90 minutes with 3H-leucine. The cells wxe then washed, and incubated Wioe for 15 minutes in 100 volunes of add leucine-rich media, a pmcedure which eliminates alrost all intracœllular TCA soluble radioadety. After these incubations levels of TCA soluble and TCA precipitable radioactivity in the cell lysates were detmdmdI and cells incubated for 120 minutes move in tm volumes of Ieucinerich media. At the end of this incubation, total Kl soluble and precipitable radioactivity was again determiraed in the œll lysate, and also in the tm hour incubaticn media. Tb total increase in TCA soluble radioactivity in the ells and their media was divided by the 0 time TCA precipitable radioactivity, to detadn...

Response of human immunodeficiency virus lymphomas to highly active anti-retroviral therapy without chemotherapy: report of four patients and literature review

We report four HIV-related lymphoma patients, and review those from eight other published studies, who responded rapidly and durably to highly-active antiretroviral therapy (HAART) alone. Nine of these patients had localized, extra-nodal lymphomas, while two had primary effusion lymphomas (PEL); eight were of B cell origin. Some HIV-related lymphomas may be effectively treated, and perhaps cured with immune reconstitution alone. Because HAART therapy markedly improves the prognosis of HIV-associated lymphomas, it is now often initiated as soon as they are diagnosed. We report four patients who responded to HAART before chemotherapy was initiated, and who have remained in remission with no other treatment. The literature review revealed a total of eight HIVinfected patients whose biopsy proven lymphomas also responded to HAART alone. Here, we report and summarize these 12 patients’ data. In three of our own patients in whom HAART preceded planned chemotherapy, rapid and complete remissions of their lymphomas occurred; a fourth patient remained in remission 6 months after total cutaneous tumor resection and HAART. Table I presents a detailed outline of each patient’s data [1–8]; patients 1–4 are those reported by us. Table II is a summary of the HIV-related data and time intervals. CD4 levels at lymphoma diagnosis were 10–92 in six patients (median 35, mean 41), and 195–256 in four patients; viral loads were 410. HAART was not initiated until lymphoma diagnosis (regimens outlined in Table I), though HIV was diagnosed as long as 27 months earlier. Two patients had primary effusion lymphomas (PEL), one Hodgkin disease (HD) and eight localized extra-nodal lymphomas (77%) (Table I) Patient no. 1 presented with an area of multi-nodular cutaneous infiltration of the abdominal wall, found to be a high grade lymphoblastic neoplasm. HAART was initiated after resection and no recurrent or additional lymphoma had developed in the ensuing 6 months. Lymphoma diagnosis was established by incisional or excisional biopsy of four peripheral masses, core needle biopsy of two lung masses and three brain masses, and cytologic analysis of the two PEL patients’ effusions. The results of marker studies are presented in Table I. CD4 levels increased after HAART by a median of 3.47 fold, while the viral loads markedly diminished (Table II). After HAART therapy, the median CD4 count of the 12 patients rose from 74 to 315/mcl, and the viral load median fell from 259 000 to 875 (Table II). The interval between HAART initiation and lymphoma response ranged from 1 to 150 weeks, with a median of 10 and mean of 24 weeks. Remission duration ranged from 1 to 36 months, with a median of 16 and a mean of 36 months (Table II). Neither our patients’ lymphomas nor those reported by others are known to have relapsed after response to HAART, and none received

Cryoglobulinemia in a patient with chronic lymphocytic leukemia - A case report and review of literature of renal involvement in CLL.

The incidence of glomerulonephritis, as a manifestation of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), has always been considered low. Though renal infiltration is usually detected at post-mortem, it does not often interfere with kidney function [1]. Though immunoglobulin (Ig) levels in most CLL patients are subnormal, small monoclonal Ig peaks are occasionally detected in serum. They were present in a number of reported CLL nephropathy patients, and not all were cryoglobulins; serum and glomerular staining were concordant for Ig type [2,3,4]. Myeloma, which secretes monoclonal light chains, causes nephropathy in 25% of patients. But the little presumably secreted by small plasma cell clones, without myeloma, may also be nephrotoxic. The same is true of the low secretory CLL cells, which may occasionally be associated with cryoglobulins and other nephrotoxic Igs [5]. We report a patient with early stage CLL (Rai stage 0) with cryoglobulins, which led to membranoproliferative glomerulonephritis (MPGN), and death. We located reports of 51 patients with CLL-associated nephrotic syndrome or nephropathy, mostly from MPGN related to local Ig deposits. In those patients screened for cryoglobulins, about half tested positive. Many were early stage cases, where MPGN developed long after CLL presentation, and responded to its treatment. As early diagnosis and treatment CLL-related nephropathy may be curative, we propose a prospective study to determine the incidence of hyperalbuminuria development after presentation.